Abstract:
A decade of research has revealed a key role for the habenula, a small structure adjacent to the thalamus, in the brain’s processing of aversive stimuli. Not only does the habenula respond to such stimuli, it also inhibits midbrain dopamine neuron firing and its stimulation can drive conditioned place avoidance. Based on these findings, many investigators have suggested that habenula hyperactivity may play a role in depression, and this hypothesis is supported by work in animal models.
However, the habenula hyperactivity hypothesis of depression has yet to be tested directly in humans, possibly due to the habenula’s small size, which makes its measurement challenging.
I will present two studies, both of which use a basic computational approach to examine the role of the habenula in humans, and whether it is hyperactive in depression. The first study (Lawson et al 2014, PNAS) showed that in healthy volunteers the habenula responds to aversively conditioned stimuli in a manner consistent with learning. As initially neutral cues became increasingly associated with painful electric shocks, habenula activation increased significantly. The second study (Lawson et al 2016, Molecular Psychiatry) showed a similar pattern in an independent sample of healthy volunteers. However, in unmedicated depressed patients habenula activation significantly decreased in response to increasing association with shocks, contradicting the hypothesis. Habenula resting-state perfusion and volume were similar between the groups, though the latter correlated negatively with anhedonic symptoms. These data suggest that the habenula does function abnormally in depression, but that the simple hyperactivity hypothesis is probably incorrect.

About CiNet’s Friday Lunch Seminars:The Friday Lunch Seminar is CiNet’s main regular meeting series, held every week at 12.15 in the beautiful main lecture theatre on the ground floor at CiNet. The talks are typically 40mins long and orientated towards an inter-disciplinary audience. They are informal, social, and most people bring their own lunch to eat during the talk. They are open to anyone who is feeling curious and wants to come, regardless of where you work.